SUMMARY: CORE B- CLINICAL CORE. The Clinical Core will support the Harvard Aging Brain Study (HABS) Program Project Grant (PPG) by retaining a diverse sample of older individuals (Aim 1), carefully evaluating them with annual neuropsychological and clinical assessments, and scheduling all procedures (Aim 2), obtaining biological fluid samples (Aim 3), facilitating brain donations (Aim 4) and providing clinical and neuropsychological expertise to all Projects (Aim 5). Individuals recruited during the first grant cycle (Wave 1: 2010-2015; n=285) now have 7-9 years of longitudinal follow-up. Individuals recruited during the second grant cycle (Wave 2: 2015-current; n=88) allowed us to replenish the cohort, expand the age range down to 50 and add a new Latino/a group. We have maintained an average attrition rate of 5.84.6% per year over nine years. Our Active Cohort now includes 290 individuals (mean age 70.69.4 years, current age range 51-94). The representation of minorities in the sample is now 22%, exceeding the proportion of older minority populations in the greater Boston area. Although participants were all clinically normal when they joined HABS, 13.2% of participants have progressed to a CDR of 0.5, with 10.3% reaching a clinical consensus diagnosis of MCI or mild dementia, and we anticipate that an increasingly proportion of the cohort individuals will decline over the next 5 years. Retention and careful evaluation of the HABS cohort is essential to achieve the scientific goals of our study. In addition to performing annual assessments of cognition, mood, social engagement, quality of life, activities of daily living and subjective cognitive concerns and scheduling imaging procedures with the Imaging Core, the Clinical Core will work with Project 2 to monitor physical activity, facilitate recruitment into the Advanced Imaging Cohort for Project 3 and assist Project 4 with training on mobile computerized assessments that will be administered in the home environment. The Clinical Core will collect biological fluid samples for biomarker and genetic studies in coordination with the Biomarker Core and facilitate discussion of brain donation and coordination of successful autopsy completion with the Massachusetts Alzheimer?s Disease Research Center?s Neuropathology Core for Project 1. Finally, the Clinical Core will ensure reliable data collection, quality control of all clinical data, and will input and transfer data to DataCentral in coordination with the Analytic Core. The Clinical Core is comprised of a seasoned group of multidisciplinary clinical investigators with specialized training in neurology, neuropsychology and neuropsychiatry, along with a dedicated staff of research assistants. The Clinical Core will facilitate the careful longitudinal characterization of HABS participants, including determination/adjudication of MCI or dementia diagnosis made by consensus with our multidisciplinary clinical investigators who are blind to biomarker status. The Clinical Core and the HABS PPG seek to improve our understanding of the aging brain, and the role of amyloid, tau and vascular pathologies that may be involved in imminent and clinically meaningful cognitive decline.